An epidemic of type 2 diabetes is present in most countries of the world. As the prevalence of type 2 diabetes increases drastically and it is associated with devastating long-term complications, there is a very strong demand for the search of dietary supplements and alternative treatments for this disease. Cordyceps sinensis (CS) is a tonic supplement and a Chinese herbal medicine, which helps the body build strength, endurance, and stamina. In addition, CS is famous for its use as an aphrodisiac for both men and women and is also used to treat various respiratory, heart, liver, and kidney diseases. This R21 application is to explore the role of CS as a dietary supplement in the treatment of type 2 diabetes and its underlying molecular mechanisms. Our preliminary data, along with results of other studies show that CS lowers blood glucose concentration in experimental diabetic animals without affecting insulin concentration. However, it is not clear through which tissue/organ CS affects glucose homeostasis and the underlying molecular mechanism remains unknown. In this exploratory R21 application, we will examine the effect of CS on glucose homeostasis in rodents by examining glucose tolerance, in vivo insulin sensitivity and insulin production in both ob/ob and control (C57BL/6J) mice to investigate the site of action for CS. In addition, we will also use isolated perfused organ techniques and microarray to explore how CS affects glucose metabolism. The primary objective of this exploratory project is to assess the feasibility of investigating the effect of CS as a dietary supplement in those with a hyperglycemic state, thereby generating preliminary results to serve as the basis of more definitive studies. This project will provide the mechanistic insights of how CS affects glucose metabolism. Our long-term goal is to establish CS as a new dietary supplement for diabetic patients. It could potentially identify a new treatment for type 2 diabetes.